Patients exhibiting acquired immune deficiency syndrome (AIDS) were first observed in 1981. While occurrences were at first isolated and appeared to be confined to the male homosexual population, this observation very quickly proved to be wrong as AIDS was found to be widespread across all population groups.
AIDS infection has been characterized as an epidemic in some parts of the world, and it is expected that other parts of the world will soon characterize the infection as such.
In U.S. Pat. No. 4,520,113, filed Apr. 23, 1984, Gallo et al. stated that the evidence suggested that "the disease spreads by the transmission of an infectious agent. The primary targets of affliction in the human body are specific subpopulations of T-cells. The severe immune deficiency of these patients results from an unusually low proposition of helper T-cells (T4) in their lymphocyte population, thus reducing the availability of many T4 helper functions, among which is the production of antibodies by B-cells".
Gallo, et. al., Science 220:865-867 (May 20, 1983) proposed that the causative agent of AIDS is a human T-cell leukemia virus (HTLV). These viruses are characterized by pronounced tropism for T4 cells, reverse transcriptase with high molecular weight (100 kd), and with preference for Mg.sup.2+ for optimal enzymatic activity. Schupbach, et al., Science 224:503-505 (May 4, 1984). The work of Barre-Sinussi, et al., Science 220:868-871 (May 20, 1983), agreed with the Gallo hypothesis, and differed only in its calling the virus lymphadenopathy AIDS associated virus (LAV). Currently, most scientists in the field refer to the virus as human immunodeficiency virus (HIV), and this term will be used hereafter.
Investigations began almost immediately for suitable methods and materials to treat HIV infections, which are always fatal. It must be pointed out that investigations proceeded on several levels. The first of these is on the "prevention" level, i.e., attempts to prevent infection from occurring. This approach involves modifying behavior patterns, and is not discussed further herein. The second approach has been investigations along the lines of developing an immune response to the virus, by way of a vaccine. Research has been slow in this area, for several reasons. HIV infections occur only in humans, and are always fatal. Vaccine research generally involves introducing an etiolated or dead strain of the virus to the subject in order to develop an immune response. Animal models do not work, and the risks involved in human trials have been too great to advance work in this field very far.
Yet a third approach has been to treat the "follow-up" infections, such as Pseudomonas carinii pneumonia (PCP), which develop after HIV devastates the immune system. Sulfamethoxazole, sold as "Bactrim" has been one effective drug. It is extremely toxic, however, and many AIDs patience have allergies to it. These factors result in limited usefulness for the drug. Where sulfamethoxazole cannot be used, pentamidine isethionate, known as an anti-protozoan, is used. This drug has proven to be somewhat more effective when administered to AIDs patients in intravenous or aerosol form, but it too is extremely toxic and has various known and suspected side effects. Long term therapy with either of these substances is not possible.
The fourth and final approach to treating HIV is via drugs which interfere with the virus' ability to replicate. This area has received much attention because, ultimately, it is the only approach which will destroy or limit the infection at its source.
The current drug of choice in this area is azidothymidine, also referred to as AZT. AZT, in severely limited trials, has been shown to interfere with viral replication, which results in some remission of the infection.
There have, however, been problems with AZT as well. It is toxic, and is suspected of suppressing bone marrow function. See, e.g. Kolata, Science 225:1463 (Mar. 20, 1987). The regime which is used for treatment with AZT requires very stringent conditions which must be followed by the patient for the drug to be effective. In view of this, as well as AZT's toxicity, research did not and has not stopped following the positive results obtained with the drug.
It is therefore an object to the invention to provide a method of treating humans infected with viruses characterized by RNA-dependent polymerases, especially those humans infected with human immuno-deficiency virus (HIV).
It is a further object of the invention to provide a composition useful in treating individuals infected with human immunodeficiency viruses.
How these as well as other objects of the invention are achieved will be made explicit by the disclosure which follows.